A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient populati...

Full description

Bibliographic Details
Main Authors: Ruth Van Daele, Britt Bekkers, Mattias Lindfors, Lars Mikael Broman, Alexander Schauwvlieghe, Bart Rijnders, Nicole G. M. Hunfeld, Nicole P. Juffermans, Fabio Silvio Taccone, Carlos Antônio Coimbra Sousa, Luc-Marie Jacquet, Pierre-François Laterre, Eric Nulens, Veerle Grootaert, Haifa Lyster, Anna Reed, Brijesh Patel, Philippe Meersseman, Yves Debaveye, Joost Wauters, Christophe Vandenbriele, Isabel Spriet
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/9/7/1543
Description
Summary:Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit’s binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (<i>p</i> = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2–4.7) mg/L under ECMO and 2.5 (1.4–3.9) mg/L without ECMO (<i>p</i> = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.
ISSN:2076-2607